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Intravesical bacille Calmette-Guerin (BCG) is indicated for the treatment and prophylaxis of carcinoma in situ of the urinary bladder and prophylaxis of primary or recurrent papillary tumours.1 All previous reports of uveitis after intravesical BCG therapy have been associated with arthritis.1–4 HLA-B27 has been positive in all cases with uveitis.1–4 We describe a patient who is HLA-B27 negative with isolated bilateral uveitis after intravesical BCG therapy.
A 70 year old man presented to the eye casualty department with a 4 day history of bilateral red, painful, and photophobic eyes. He had no systemic complaints. He had no ophthalmic history of note. He had a medical history of hypertension, gout, and recurrent papillary transitional cell carcinoma of the bladder. Eight weeks previously he had been seen by a urologist for haematuria and increased frequency. A diagnosis of recurrent papillary cell carcinoma was made by cystoscopy and biopsy. A 6 week course of weekly intravesical BCG therapy was commenced. His medications on presentation were Adalat (nifedipine) and amlodipine. He was allergic to penicillin and aspirin.
On ocular examination his visual acuities were 6/12 right eye and 6/6 left eye. A diagnosis was made of bilateral acute anterior uveitis. He had 2+ cells and posterior synechiae bilaterally. No keratic precipitates were seen. He had a right sided epiretinal membrane.
Laboratory studies showed an erythrocyte sedimentation rate of 66 with the rest of haematological studies normal. Biochemistry showed a raised sodium, urea, and creatinine, which were longstanding. Tests for antinuclear antibodies and rheumatoid factor were negative. Angiotensin converting enzyme was normal and Treponema pallidum antibodies were not detected. HLA-B27 was negative. Chest and pelvis radiographs were normal. His uveitis resolved completely on topical steroid therapy and mydriatics. There was no recurrence of his uveitis over the subsequent follow up period of 3 months.
There have been no reported cases of intravesical BCG causing isolated uveitis in a patient that is HLA-B27 negative. There have been 26 reported cases of reactive arthritis secondary to intravesical BCG.2 About 8% of these cases were associated with uveitis.2 All the reported cases of combined arthritis and uveitis were HLA-B27 positive.1,3,4 In the BCG related arthritides the mean time of presentation was 10.5 days after the last BCG therapy.2 Our patient started having ocular symptoms 10 days after his last BCG therapy.
In a review of 1278 patients treated with intravesical BCG for bladder cancer, 95% had no complications.5 There were no reported cases of uveitis. Arthritis and arthralgia accounted for 0.5% of the complications.5
There has been one reported case of endophthalmitis from Mycobacterium bovis-BCG used to treat bladder cancer.6 This was proved microbiologically and histologically. This presentation was delayed with the patient presenting 14 months after his last intravesical BCG therapy.
Intravesical BCG contains live attenuated mycobacteria. The intravesical BCG promotes a local acute inflammatory and subacute granulomatous reaction with macrophage and lymphocyte infiltrates in the superficial bladder.7 The exact mechanism of action is unknown but the antineoplastic effect seems to be T lymphocyte dependent.7 This enhanced cell mediated immunity results in recognition and suppression of neoplastic cells.8
It has been hypothesised that the systemic inflammatory response is seen as part of an immune response initiated by BCG and then continued by cross reactivity with particular host proteins presented by the class I MHC receptor.9
It is impossible to definitively prove that intravesicular BCG caused our patient's bilateral anterior uveitis. The possibility of an infective aetiology by active mycobacterium must also be considered. If this were the case definitive diagnosis could have been established by sending a specimen of aqueous for acid fast staining, culture, and polymerase chain reaction (PCR).6
It is plausible that intravesicular BCG can cause acute inflammatory and hypersensitivity reactions in the eye secondary to a systemic inflammatory response.1–5 Contrary to previous thought, HLA-B27 need not be a determining factor for uveitis associated with intravesicular BCG.3 This is the first reported case of isolated bilateral anterior uveitis presumed secondary to intravesicular BCG in a patient who is HLA-B27 negative.